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Description of key information

Propylene dinonanoate (CAS 41395-83-9) is a liquid mono-constituent substance with low volatility(vapour pressure 1.4E-005 Pa at 20 °C) and a log Pow of 7.7. The substance will be hydrolysed within the gastrointestinal tract. The hydrolysis products (the respective C9 fatty acid and propylene glycol) are predicted to be readily absorbed via the oral route. The fatty acid will most likely be re-esterified to triglycerides after absorption and transported via chylomicrons. The absorbed propylene glycol is readily distributed throughout the organism, oxidised to lactate aldehyde and further to lactate. The major metabolic pathway for linear fatty acids is the beta-oxidation pathway for energy generation. Absorption of propylene dinonanoate via inhalation and dermal route is expected to be low. The excretion will mainly be as CO2in expired air; with a smaller fraction of biliary excretion via the faeces due to low water solubility. No bioaccumulation will take place, as excess lactate and triglycerides are stored and used as energy need rises.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Basic toxicokinetics

In accordance with Annex VIII, Column 1, Section 8.8.1, of Regulation (EC) No 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017), assessment of the toxicokinetic behaviour of propylene dinonanoate (CAS 41395-83-9) is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physico-chemical and toxicological properties according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2017) and taking into account further available information on source substances.

There are no studies available in which the toxicokinetic behaviour of propylene dinonanoate (CAS 41395-83-9) has been investigated.

The substance propylene dinonanoate (CAS 41395-83-9) is a mono-constituent substance specified by C9 (≥ 80%) linear fatty acids diester with 1,2-propanediol.

Propylene dinonanoate (CAS 41395-83-9) is a liquid at 20 °C with a molecular weight of 356.54 g/mol. Experimental data on water solubility are not yet available (for details refer to IUCLID section 4.8). For the purpose of this assessment water solubility was estimated by Dermwin v2.02 to be 1.51e-006 mg/cm³; and therefore water solubility is considered to be < 0.1 mg/L. The calculated log Pow value is 7.7 (Vega v1.1.3 partition coefficient (Meylan/Kowwin model) calculation) and the vapour pressure is calculated to be 1.4E-005 Pa at 20 °C (SPARC v4.6).


Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log Pow) value and the water solubility. The log Pow value provides information on the relative solubility of the substance in water and lipids (ECHA, 2017).


In general, molecular weights below 500 and log Pow values between -1 and 4 are favourable for absorption via the gastrointestinal (GI) tract, provided that the substance is sufficiently water soluble (> 1 mg/L). Lipophilic compounds may be taken up by micellar solubilisation by bile salts, but this mechanism may be of particular importance for highly lipophilic compounds (log Pow > 4), in particular for those that are poorly soluble in water (≤ 1 mg/L) as these would otherwise be poorly absorbed (Aungst and Shen, 1986; ECHA, 2017).

When assessing the potential of propylene dinonanoate (CAS 41395-83-9) to be absorbed in the gastrointestinal (GI) tract, it has to be considered that fatty acid esters will undergo to a high extent hydrolysis by ubiquitous expressed GI enzymes (Lehninger, 1993; Mattson and Volpenhein, 1972; National technical information service, 1973). Thus, due to the hydrolysis the predictions based upon the physico-chemical characteristics of the intact parent substance alone may no longer apply but also the physico-chemical characteristics of the breakdown products of the ester; the alcohol propylene glycol and the corresponding fatty acid with an odd number of carbons (C9).

The estimated low water solubility (< 0.1 mg/L) and the high log Pow value > 7 of the parent compound indicate that absorption may be limited by the inability to dissolve into GI fluids. However, mi-cellular solubilisation by bile salts may enhance absorption, a mechanism which is especially of importance for highly lipophilic substances with log Pow > 4 and low water solubility (Aungst and Shen, 1986). Regarding molecular weight, the breakdown products propylene glycol (76.09 g/mol) and nonanoic acid (158.24 g/mol, respectively) are generally favourable for absorption. The alcohol component propylene glycol is highly water-soluble and has a low molecular weight and can therefore dissolve into GI fluids. Thus, propylene glycol will be readily absorbed through the GI tract (ATSDR, 1997; National technical information service, 1973). The highly lipophilic fatty acids are absorbed by micellar solubilisation.

Rodent studies on acute oral toxicity of propylene dinonanoate (CAS 41395-83-9) showed no signs of systemic toxicity resulting in LD50 values greater than 5000 mg/kg bw in rats and mice.

Analogue substance data on repeated dose toxicity were available: in a sub-chronic oral toxicity study with decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) in rats no adverse systemic effects were found, resulting in a NOAEL ≥ 1000 mg/kg bw/day. In a short-term (28-day) oral repeated dose study in rats with fatty acids, C6-12, esters with propylene glycol (CAS 85883-73-4) the NOAEL was found to be 2500 mg/kg bw/day.

The lack of systemic toxicity of the source substances cannot be equated with a lack of absorption but indicates a low toxic potential of glycol esters and the breakdown products themselves.


There are no data available on dermal absorption or on acute dermal toxicity of propylene dinonanoate (CAS 41395-83-9). On the basis of the following considerations, the dermal absorption of the substance is considered to be low.

To partition from the stratum corneum into the epidermis, a substance must be sufficiently soluble in water. Thus, with an estimated water solubility < 1 mg/L, dermal uptake of the substance is likely to be low. In addition, for substances having an octanol/water partition coefficient above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and thus limit absorption across the skin. Furthermore, uptake into the stratum corneum itself may be slow (ECHA, 2017).

The dermal permeability coefficient (Kp) can be calculated from log Pow and molecular weight (MW) applying the following equation described in US EPA (2012):

log(Kp) = -2.80 + 0.66 log Pow – 0.0056 MW

QSAR calculations using Dermwin v2.02 confirmed this assumption with a low dermal flux rate of 2.12E-5 mg/cm² per h calculated indicating only low dermal absorption potential for Propylene dinonanoate (CAS 41395-83-9) (please refer to Table 1, Dermwin v2.02, EpiSuite 4.1; 2017).

Table 1: Dermal absorption values for the components of propylene dinonanoate (CAS 41395-83-9) (calculated with Dermwin v 2.02, EpiSuite 4.1)


Structural formula

Estimated water solubility [mg/cm³]

Flux (mg/cm²/h)

Propylene dinonanoate




Skin irritation studies in rabbits with propylene dinonanoate (CAS 41395-83-9) with the neat test item and exposure duration of 4h or 23h under occlusive conditions showed no irritating effects to intact skin.

Propylene glycol esters are known to enhance the penetration of drugs through human and animal skin (CIR, 2014). Propylene dinonanoate (also named propylene glycol dipelargonate) increased the dermal penetration of [3h(g)] heparin sodium salt, thiocolchicoside, and caffeine but not testosterone.

Overall, taking into account the physico-chemical properties of propylene dinonanoate (CAS 41395-83-9), the QSAR calculations and available toxicological data, the dermal absorption potential of the substance is anticipated to be low.


Propylene dinonanoate (CAS 41395-83-9) is a liquid with a very low calculated vapour pressure of 1.4E-005 Pa at 20 °C and therefore a low volatility. Under normal use and handling conditions, inhalation exposure and the availability for respiratory absorption of the substance in the form of vapours, gases, or mists is considered to be limited (ECHA, 2017).

Based on the physical state and the physico-chemical properties of propylene dinonanoate (CAS 41395-83-9), absorption via the lung is expected to be of no toxicological concern.

Distribution and accumulation

Distribution of a compound within the body depends on the physico-chemical properties of the substance; especially the molecular weight, the lipophilic character and the water solubility. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues (ECHA, 2017).

As the parent compound propylene dinonanoate (CAS 41395-83-9) is expected to be hydrolysed prior to absorption, the distribution of the intact substance is most likely less relevant than the distribution of the breakdown products. The absorbed products of hydrolysis, propylene glycol and the respective fatty acid moieties can be distributed within the body.

The alcohol propylene glycol has a low molecular weight and high water solubility. Based on the physico-chemical properties, propylene glycol will be distributed within the body (ICPS, 1997). After absorption, propylene glycol will enter the blood circulating system through which it will be distributed within the body. In fasted animals, propylene glycol was shown to disappear rapidly from the blood most probably due to entry in the carbohydrate cycle (National technical information service, 1973). Substances with high water solubility like propylene glycol do not have the potential to accumulate in adipose tissue due to its low log Pow.

Fatty acids may be re-esterified with glycerol into triacylglycerides (TAGs) and transported via chylomicrons or absorbed from the small intestine directly into the bloodstream and transported to the liver. Via chylomicrons, fatty acids are transported via the lymphatic system and the blood stream to the liver and to extrahepatic tissue for storage e.g. in adipose tissue (Stryer, 1994).

Accumulation of the fatty acids in triglycerides in adipose tissue or the incorporation into cell membranes is possible as further described in the metabolism section below. At the same time, fatty acids may also be used for energy generation. Thus, stored fatty acids underlie a continuous turnover as they are permanently metabolised and excreted. Bioaccumulation of fatty acids only takes place, if their intake exceeds the caloric requirements of the organism.

In summary, the available information on propylene dinonanoate (CAS 41395-83-9) indicates that no significant bioaccumulation of the parent substance in adipose tissue is expected. The possible hydrolysis products, propylene glycol and the respective fatty acids will be distributed within the organism.


Metabolism of propylene dinonanoate (CAS 41395-83-9) initially occurs via stepwise enzymatic hydrolysis of the ester resulting in the corresponding monoesters (e.g. propylene glycol mono-nonanoate), the fatty acids moiety (C9) and propylene glycol.

In vitro studies with propylene glycol distearate (PGDS) demonstrated hydrolysis of the ester (Long et al., 1958). The hydrolysis of fatty acid esters in-vivo was studied in rats dosed with fatty acid esters containing one, two (like propylene glycol esters) or three ester groups. The studies showed that fatty acid esters with two ester groups are rapidly hydrolysed by ubiquitously expressed esterases and almost completely absorbed (Mattson and Volpenhein, 1968; 1972). Furthermore, the in-vivo hydrolysis of propylene glycol distearate (PGDS), a structurally related glycol ester, was studied using isotopically labelled PGDS (Long et al., 1958). Oral administration of PGDS showed intestinal hydrolysis into propylene glycol monostearate, propylene glycol and stearic acid confirming above discussed metabolism of propylene dinonanoate (CAS 41395-83-9), as well.

Following hydrolysis, absorption and distribution of the alcohol component, propylene glycol will enter the carbohydrate cycle (National technical information service, 1973). In what is considered to be the main pathway of propylene glycol metabolism in mammals, propylene glycol is oxidised by alcohol dehydrogenase to lactate aldehyde, then to lactate by aldehyde dehydrogenase. The lactate is further metabolised to pyruvate, carbon dioxide, and water. Lactate also contributes to glucose formation through gluconeogenic pathways. Lactate, via phosphoenol pyruvate, can be transformed into glucose and stored as glycogen (EMA, 2014).

In the liver, fatty acids can be metabolised in phase I and II metabolism.

An important metabolic pathway for fatty acids is the beta-oxidation for energy generation. In this multi-step process, the fatty acids are at first esterified into acetyl-CoA derivatives and subsequently transported into cells and mitochondria by specific transport systems. Following absorption into the intestinal lumen, fatty acids are re-esterified with glycerol to triglycerides and included into chylomicrons for transportation via the lymphatic system and the blood stream to the liver. In the next step, the acetyl-CoA derivatives are broken down into acetyl-CoA molecules by sequential removal of 2-carbon units from the aliphatic acetyl-CoA molecule. Further oxidation via the citric acid cycle leads to the formation of H2O and CO2 (Lehninger, 1993; Stryer, 1994).

The endpoint of metabolism of odd-chain fatty acids is propionyl-CoA as opposed to acetyl-CoA. Propionyl-CoA is converted into succinyl-CoA and can enter into the citric acid cycle like acetyl-CoA. For nonanoic acid complete catabolism for energy supply or conversion to fat suitable for storage is expected (Nonanoic acid (PT2), Assessment report, 2013).

Available in vitro data on genotoxicity of propylene dinonanoate (CAS 41395-83-9) do not show any genotoxic properties. In particular, an Ames test (key study, 2018), an in-vitro cytogenicity/micronucleus test (key study, 2018) and an in-vitro mammalian gene mutation assay (key study, 2017) with propylene dinonanoate (CAS 41395-83-9) were consistently negative and therefore no indication of reactivity is indicated.


Based on the metabolism described above, propylene dinonanoate (CAS 41395-83-9) and its breakdown products will be metabolised in the body to a high extent. In-vivo studies with propylene glycol distearate (PGDS) showed that 94% of the labelled PGDS was recovered from 14CO2 excretion and only ~ 0.4% of the total dose of PGDS was excreted in the urine after 72 h supporting this notion as well (Long et al., 1958). A similar observation was made for propylene glycol, which was excreted in substantial amounts as 14CO2 during the first 24 h after administration of radioactive label (National technical information service, 1973).

The fatty acid component will be metabolised for energy generation or stored as lipid in adipose tissue or used for further physiological properties e.g. incorporation into cell membranes (Lehninger, 1993; Stryer, 1994). Therefore, the fatty acid component is not expected to be excreted to a significant degree via the urine or faeces but excreted via exhaled air as CO2 or stored as described above. As propylene glycol will be highly metabolised as well, the primary route of excretion will be via exhaled air as CO2 (ATSDR, 1997).


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